Right heart failure after left ventricular assist device: From mechanisms to treatments.

Left ventricular assist device (LVAD) therapy is a lifesaving option for patients with medical therapy-refractory advanced heart failure. Depending on the definition, 5-44% of people supported with an LVAD develop right heart failure (RHF), which is associated with worse outcomes. The mechanisms related to RHF include patient, surgical, and hemodynamic factors. Despite significant progress in understanding the roles of these factors and improvements in surgical techniques and LVAD technology, this complication is still a substantial cause of morbidity and mortality among LVAD patients. Additionally, specific medical therapies for this complication still are lacking, leaving cardiac transplantation or supportive management as the only options for LVAD patients who develop RHF. While significant effort has been made to create algorithms aimed at stratifying risk for RHF in patients undergoing LVAD implantation, the predictive value of these algorithms has been limited, especially when attempts at external validation have been undertaken. Perhaps one of the reasons for poor performance in external validation is related to differing definitions of RHF in external cohorts. Additionally, most research in this field has focused on RHF occurring in the early phase (i.e., ≤1 month) post LVAD implantation. However, there is emerging recognition of late-onset RHF (i.e., > 1 month post-surgery) as a significant cause of morbidity and mortality. Late-onset RHF, which likely has a unique physiology and pathogenic mechanisms, remains poorly characterized. In this review of the literature, we will describe the unique right ventricular physiology and changes elicited by LVADs that might cause both early- and late-onset RHF. Finally, we will analyze the currently available treatments for RHF, including mechanical circulatory support options and medical therapies.

Long-Term Outcomes and Risk Stratification of Patients With Heart Failure With Recovered Ejection Fraction.

This study aimed to understand the long-term outcomes of patients with heart failure with recovered ejection fraction, identify predictors of adverse events, and develop a risk stratification model. From an academic healthcare system, we retrospectively identified 133 patients (median age 66, 38% female, 30% ischemic etiology) who had an improvement in left ventricular ejection fraction (LVEF) from <40% to ≥53%. Significant predictors of all-cause mortality, hospitalization, and future reduction in LVEF were identified through Cox regression analysis. Kaplan-Meier survival was 70% at 5 years. Freedom from hospitalization was 58% at 1 year, and the risk of future LVEF reduction to <40% was 28% at 3 years. Diuretic dose and B-type natriuretic peptide (BNP) at the time of LVEF recovery were the strongest predictors of mortality and hospitalization in multivariate-adjusted analysis (BNP hazard ratio 1.13 per 100 pg/ml increase [p <0.01]; furosemide-equivalent dose hazard ratio 1.19 per 40 mg increase [p = 0.02]). An all-cause mortality Cox proportional hazard risk model incorporating New York Heart Association functional class, BNP and diuretic dose at the time of recovery showed excellent risk discrimination (c-statistic 0.79) and calibration. In conclusion, patients with heart failure with recovered ejection fraction have heterogenous clinical outcomes and are not "cured." A risk model using New York Heart Association functional class, BNP, and diuretic dose can accurately stratify mortality risk.

Echocardiographic imaging of temporary percutaneous mechanical circulatory support devices.

Cardiogenic shock is a state of end-organ hypoperfusion due to primary cardiac dysfunction and portends a poor prognosis. Shock refractory to inotropic and vasopressor support is often an indication for mechanical circulatory support. When mechanical support device complications or malfunction arise, echocardiography offers rapid assessment of device position and function. Repositioning can be done under echocardiographic guidance. Despite the widespread use of percutaneous mechanical circulatory support, there is a dearth of information regarding echocardiography as it pertains to these devices. In this review, we discuss the utility of echocardiography with percutaneous mechanical circulatory support devices.

Implications of cancer prior to and after heart transplantation.

Cancer and cardiovascular disease share many risk factors. Due to improved survival of patients with cancer, the cohort of cancer survivors with heart failure referred for heart transplantation (HT) is growing. Specific considerations include time interval between cancer treatment and HT, risk for recurrence and risk for de novo malignancy (dnM). dnM is an important cause of post-HT morbidity and mortality, with nearly a third diagnosed with malignancy by 10 years post-HT. Compared with the age-matched general population, HT recipients have an approximately 2.5-fold to 4-fold increased risk of developing cancer. HT recipients with prior malignancy show variable cancer recurrence rates, depending on years in remission before HT: 5% recurrence if >5 years in remission, 26% recurrence if 1-5 years in remission and 63% recurrence if <1 year in remission. A myriad of mechanisms influence oncogenesis following HT, including reduced host immunosurveillance from chronic immunosuppression, influence of oncogenic viruses, and the cumulative intensity and duration of immunosuppression. Conversely, protective factors include acyclovir prophylaxis, use of proliferation signal inhibitors (PSI) and female gender. Management involves reducing immunosuppression, incorporating a PSI for immunosuppression and heightened surveillance for allograft rejection. Cancer treatment, including immunotherapy, may be cardiotoxic and lead to graft failure or rejection. Additionally, there exists a competing risk to reduce immunosuppression to improve cancer outcomes, which may increase risk for rejection. A multidisciplinary cardio-oncology team approach is recommended to optimise care and should include an oncologist, transplant cardiologist, transplant pharmacist, palliative care, transplant coordinator and cardio-oncologist.

Pharmacologic Inhibition of Pain Response to Incomplete Vascular Occlusion Blunts Cardiovascular Preconditioning Response.

Complete vascular occlusion to distant tissue prior to an ischemic cardiac event can provide significant cardioprotection via remote ischemic preconditioning (RIPC). Despite understanding its mechanistic basis, its translation to clinical practice has been unsuccessful, likely secondary to the inherent impossibility of predicting (and therefore preconditioning) an ischemic event, as well as the discomfort that is associated with traditional, fully occlusive RIPC stimuli. Our laboratory has previously shown that non-occlusive banding (NOB) via wrapping of a leather band (similar to a traditional Jewish ritual) can elicit an RIPC response in healthy human subjects. This study sought to further the pain-mediated aspect of this observation in a mouse model of NOB with healthy mice that were exposed to treatment with and without lidocaine to inhibit pain sensation prior to ischemia/reperfusion injury. We demonstrated that NOB downregulates key inflammatory markers resulting in a preconditioning response that is partially mediated via pain sensation.

Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis.

Emerging data in mice and humans reveals a critical contribution of Th17-associated cytokines, particularly interleukin-(IL)-23 and IL-17, in the pathogenesis of psoriasis. The IL-23/Th17 pathway is a therapeutic target for biologic agents and systemic therapies in psoriasis treatment. A literature search was performed to review and summarize the current evidence on IL-17 and IL-23 as a basis for understanding the use of anti-IL-17 and anti-IL-23 agents for psoriasis therapy. Using PubMed, recent articles were identified pertaining to IL-17, IL-23, and psoriasis. Signaling via the heterodimeric IL-23 receptor induces production of IL-17, which stimulates production of proinflammatory keratinocyte cytokines that mediate the psoriatic response. An overexpression of IL-23, IL-17, or Th17 cells in transgenic mice is associated with the development of inflammatory disease. Both IL-17 knockout mice and humans with a genetic IL-17 deficiency are susceptible to extracellular and intracellular pathogens. This suggests a potential for adverse effects from clinical administration of anti IL-23-p40/IL-17 therapies. Anti-p40 antibodies, briakinumab and ustekinumab, were tolerated in clinical trials and substantially improved psoriasis. Further trials of anti IL-17 therapies are needed to assess their clinical use and potential for infection and other adverse events.

Palliative cancer care ethics: principles and challenges in the Indian setting.

Palliative cancer treatment is a system of care that seeks to relieve suffering in patients with progressive cancer. Given the intractable symptoms with which certain malignancies manifest, palliative care offers a practical approach towards improving the patient's quality of life. However, there are an array of ethical issues associated with this treatment strategy such as particular methods of pain relief, a reliable assessment of suffering, autonomy, and multi-specialist care. While these principles are important to increase and improve the network of palliative care, the resource-poor Indian environments present numerous barriers for these principles to be practically applied. As the infrastructure of comprehensive cancer centers develop, paralleled with an increase in training of palliative care professionals, significant improvements need to be made in order to elevate the status of palliative cancer care in India.